rs104886488

Positions:

• chr7-151186916-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001142459.2(ASB10):​c.215G>A​(p.Arg72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,613,916 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (7 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts P:1 B:2 O:1
• Conservation: PhyloP100: 0.383

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066768825).
• BP6: Variant 7-151186916-C-T is Benign according to our data. Variant chr7-151186916-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 50954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 264 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.215G>A	p.Arg72His	missense_variant	1/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_001142460.1	c.215G>A	p.Arg72His	missense_variant	1/5		NP_001135932.2
ASB10	NM_080871.4	c.272-257G>A		intron_variant			NP_543147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.215G>A	p.Arg72His	missense_variant	1/6	1	NM_001142459.2	ENSP00000391137.2

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 264 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00179 AC: 446 AN: 248998 Hom.: 4 AF XY: 0.00184 AC XY: 248 AN XY: 134900

Gnomad AFR exome AF: 0.000744

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.00328

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00247 AC: 3603 AN: 1461584 Hom.: 7 Cov.: 35 AF XY: 0.00236 AC XY: 1715 AN XY: 727096

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.00304

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152332 Hom.: 1 Cov.: 33 AF XY: 0.00164 AC XY: 122 AN XY: 74476

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00315

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00269 Hom.: 1

Bravo AF: 0.00171

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00360 AC: 31

ExAC AF: 0.00205 AC: 249

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00196

EpiControl AF: 0.00249

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1 Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glaucoma 1, open angle, F Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 15, 2012	- -
not provided, no classification provided	literature only	Casey Eye Institute Glaucoma Genetics Lab	-	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 23, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.033
Sift	Uncertain	0.025	D;D
Sift4G	Benign	0.098	T;T
Polyphen		0.027	.;B
Vest4		0.20
MVP		0.15
MPC		0.058
ClinPred		0.0013	T
GERP RS		1.5
Varity_R		0.049
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs104886488; hg19: chr7-150884003; COSMIC: COSV104997140; COSMIC: COSV104997140;